Ganoderma lucidum inhibits proliferation of human ovarian cancer cells by suppressing VEGF expression and up-regulating the expression of connexin 43
Ganoderma lucidum inhibits proliferation of human ovarian cancer cells by suppressing VEGF expression and up-regulating the expression of connexin 43
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DOI：
10.1186/1472-6882-14-434
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发表时间：
2014-12-05
影响因子：
--
通讯作者：
Wang, Ning
中科院分区：
文献类型：
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作者：
Dai, Shuyan;Liu, Jingjing;Wang, Ning
背景：灵芝（G. lucidum，Reishimax）是一种已知对肿瘤细胞生长具有抑制作用的草药蘑菇。然而，其抗卵巢癌增殖作用的分子机制尚未完全阐明。方法：用灵芝处理人卵巢癌细胞HO 8910（HOCC）和人原代卵巢细胞（HPOC）。采用MTT法研究灵芝处理对细胞增殖的影响。通过免疫组织化学和实时聚合酶链反应检测血管内皮生长因子（VEGF）和连接蛋白43（Cx43）的表达。为了研究CX43介导的抗肿瘤活性的分子机制，使用小干扰RNA（siRNA）来敲低HOCC中Cx43的表达。结果：灵芝处理导致HOCC增殖减少。增殖抑制伴随着癌细胞中 VEGF 表达的减少和 Cx43 表达的增加。癌细胞中 Cx43 或 VEGF 的免疫反应程度与用于治疗的灵芝浓度相关。此外，敲低HOCC中Cx43的表达消除了灵芝对细胞增殖的影响，但不改变灵芝诱导的VEGF表达的减弱。结论：灵芝通过下调VEGF的表达和上调下游Cx43的表达来抑制卵巢癌。灵芝可能是治疗卵巢癌的有前途的治疗剂。
Background: Ganoderma lucidum (G. lucidum, Reishimax) is an herbal mushroom known to have inhibitory effect on tumor cell growth. However, the molecular mechanisms responsible for its anti-proliferative effects on the ovarian cancer have not been fully elucidated.Methods: Human ovarian cancer cells HO 8910 (HOCC) and human primary ovarian cells (HPOC) were treated with G. lucidum. Effects of G. lucidum treatment on cell proliferation were studied by MTT assay. The expression of vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) were measured by immunohistochemistry and real time polymerase chain reaction. To study the molecular mechanism of CX43 mediated anti-tumor activity, small interference RNA (siRNA) was used to knockdown Cx43 expression in HOCC.Results: G. lucidum treatment resulted in reduced proliferation of HOCC. Inhibition of proliferation was accompanied by a decrease in VEGF expression and increase in Cx43 expression in the cancer cells. The extent of immune-reactivity of Cx43 or VEGF in cancer cells were correlated with the concentrations of G. lucidum used for treatment. Furthermore, knockdown of Cx43 expression in HOCC abrogated the effect of G. lucidum on cell proliferation without alteration of G. lucidum-induced attenuation of VEGF expression.Conclusions: G. lucidum inhibits ovarian cancer by down-regulating the expression of VEGF and up-regulating the downstream Cx43 expression. G. lucidum may be a promising therapeutic agent for the treatment of ovarian cancer.